Helen R. Strausser

Prostaglandins and the immune response.

Abstract The experimental evidence amply demonstrates that exogenous Pg is capable of inhibiting most immunological functions. The physiological role of Pgs in immune cell regulation, however, remains unresolved. This uncertainty arises from the fact that although Pgs are normally found in tissues in nanogram quantities or less, many experiments which demonstrate Pg mediated immune cell inhibition usually employ quantities at least one thousand- fold larger. In such experiments, the results, obviously reflect pharmacological rather than physiological effects. In view of the literature reviewed here, the following statements summarize the evidence which implicate Pg in a physiological role: 1. A. Pgs inhibit immune cell responsiveness. 2. B. Immune and non-immune cells secrete Pgs in response to various stimuli. 3. C. Immune cells possess receptors for Pgs. 4. D. Indomethacin enhances immune function in tumor-bearing and antigen-challenged mice. The recent indications that Pgs may mediate their effects through the cyclic endoperoxides and non-prostanoate metabolites may prove to be an important challenge to the many proposed roles of Pgs. At this time, no definitive evidence exists that compounds other than the classical Pgs are active in immune cell inhibition.

Immune system modulation and its effect on the blood pressure of the spontaneously hypertensive male and female rat

Abstract Spontaneously hypertensive rats (SHR) demonstrate a consistently lower immune response to Con A as compared to Wistar Kyoto ( W K ). Using antithymocyte serum, T and B cell responses of SHR drop considerably while blood pressures decrease to normal levels. Levamisole treatment has little or no effect on mitogen responses, but depresses blood pressure of SHR. It is hypothesised that hypertension in SHR is autoimmune in nature.

Prostaglandins and cyclic nucleotides in moloney sarcoma tumors

Abstract A 53-fold increase in the amount of prostaglandin E as well as a 7-fold increase in the amount of prostaglandin F was found associated with virus-induced Moloney sarcoma tumors when compared with the amounts found in normal leg muscles from weanling BALB/c mice. There was a concomitant 2-fold increase in the concentration of cyclic AMP, however, no significant change in the concentration of cyclic GMP was observed. Prostaglandin E 1 stimulated cyclic AMP formation in tumor tissue incubated in vitro . The tumor tissue continued to synthesize relatively large amounts of prostaglandin E during a 3 hr. incubation. The prostaglandins were primarily recovered in the incubation medium and not retained in the tissue. Indomethacin, an established prostaglandin synthetase inhibitor, prevented the synthesis. Arachidonic acid and dibutyryl-cyclic AMP failed to stimulate this synthesis. The prostaglandin of the E series associated with the tumor was identified as prostaglandin E 2 by thin layer chromatography.

Effects of Sex Hormones on Some T and B Cell Functions, Evidenced by Differential Immune Expression Between Male and Female Mice and Cyclic Pattern of Immune Responsiveness During the Estrous Cycle in Female Mice*

ABSTRACT: The responses of spleen cells from male and female BALB/c mice were evaluated to determine if sex‐related variations in immune expression could be found. The immunologic assays used included blastogenic responses to mitogens, and direct and indirect measurement of plaque‐forming cells against particulate antigens. The results indicated that responses of spleen cells from young adult female mice were higher than those of males in all comparative tests. Newborn mice did not demonstrate the sex‐associated immune differences; and among the weanling mice slight differences between male and female spleen cells responsiveness to mitogenic agents were observed.

Effects of indomethacin on Moloney sarcoma virus-induced tumors.

Abstract Chronic administration of indomethacin to weanling (20 day old) BALB/c mice inoculated with Moloney sarcoma virus (MSV) delayed the onset of the tumor and suppressed the tumor growth. As expected, the prostaglandin (PG) levels associated with the MSV-injected leg muscle of the indomethacin treated mice were greatly depressed when compared to the elevated PG content associated with the tumors of MSV injected control mice. There was no effect of indomethacin on the cyclic AMP or cyclic GMP levels. The elevated levels of PG and cyclic AMP associated with the tumor were found to parallel the tumor growth. Administration of antilymphocyte serum (ALS) to the mice at the time of MSV inoculation resulted in accelerated and enhanced tumor growth. Indomethacin treatment of these mice similarly suppressed the tumor growth, but less dramatically.

Physiological consequences of β-adrenoceptor desensitization in guinea pigs

Abstract The effects of repetitive doses of β-adrenoceptor stimulants on the resting tone and responsiveness of broncho-pulmonary smooth muscle were studied in guinea pigs. Collapse time was used to assess bronchospasm in conscious animals while resistance and compliance measurements were used in the anesthetized guinea pigs. Repetitive administration of either isoproterenol or salbutamol, at effective bronchodilator doses, caused an exacerbation of the histamine-induced bronchospasm in the presence or absence of anesthesia. Repetitive administration of either prostaglandin E 1 , 20 μg/kg i.m., or aminophylline, 400 μg/kg i.m. did not enhance histamine-induced bronchospasm. Furthermore, in guinea pigs preselected for lack of histamine sensitivity, treatment with salbutamol caused a decrease in both dynamic compliance values and peak expiratory flow rate as well as an increase in resistance values. Trachea removed from guinea pigs treated with isoproterenol or salbutamol retained normal responsiveness to histamine and dibutyryl cAMP while the responsiveness to isoproterenol was reduced. These studies indicate that repetitive administration of β-adrenoceptor stimulants can produce a specific desensitizatio of β-adrenoceptors in pulmonary tissue and an alteration of resting baseline values of pulmonary mechanics measurements.

Stimulation of the hemagglutinin response of aged mice by cell-free lymphoid tissue fractions and bacterial endotoxin

Abstract Hemagglutinin titers to sheep red blood cells (SRBC) have been measured in CF1/S female mice between 5 weeks and 18 months of age. The response was low at 5 weeks, peaked at 3 months and decreased thereafter. At 18 months of age the titers were as low as at 5 weeks. Treatment of the aged mice with cell-free acetone powder fractions of calf thymus and spleen significantly augmented the immune responsiveness to SRBC. A similar increase in antibody titers in aged mice was seen with small amounts (1 ng) of a lipopolysaccharide endotoxin prepared from Salmonella enteriditis, but not with ovalbumin. The results of this study indicate that the depressed hemagglutinin response observed in aged mice is not finite and can be augmented by the administration of various lymphoid tissue fractions or by endotoxin.

Sex-Related Immunocompetence of BALB/C Mice: II. Study of Immunologic Responsiveness of Young, Adult and Aged Mice

Abstract The immune responsiveness of male and female BALB/CJ mice from 2 months to 2 years of age was determined by spleen cell responses to mitogens and mixed lymphocyte reactivity. T cell responses of 3 month to 1 year old female mice were greater than those of the males at the same ages. The female B cell response remained higher than males throughout the entire period tested (2 years) but T cell reactivity of males was consistently superior after 14 months of age. A substrain BALB/ CAnNCrlBr did not demonstrate significant sex differential in immune responses and the T cell reactivity of these mice at 1 to 2 years of age was between 25 and 50% higher than that of the BALB/CJ mice. Prostaglandin E levels of spleen cell cultures from both substrains were measured by radioimmunoassay. The levels of the BALB/CAnNCrlBr were approximately 50% lower than the amount measured for BALB/CJ mice. These levels increased with age in both substrains. Comparing many factors, it is hypothesized that prostaglandin E, an immunosuppressive agent, may be a principal cause of the substrain, the sex and the age differential.

Lymphokines secreted from sodium periodate-treated lymphocytes

Abstract This study was designed to determine if sodium metaperiodate (NaIO 4 )-treated lymphocytes secrete lymphokines and if these lymphokines are similar to those obtained from mitogen- or antigen-stimulated lymphocytes. A brief exposure of CBA spleen cells to NaIO 4 induced the secretion of significant amounts of migration inhibitory factor (MIF). This MIF had a molecular weight range between 30,000 and 58,000, and was stable when heated at 56 °C for 30 min, but unstable at 80 °C. These characteristics are similar to those previously reported for mitogen- and antigen-induced MIF. In addition, NaIO 4 induced the secretion of lymphotoxin (LT) from CBA and Balb/c spleen cells, as well as from guinea pig lymph node cells. NaIO 4 was compared to the other inducers in regard to the quantity of LT secreted. Supernatant derived from NaIO 4 -treated mouse spleen cells contained less LT than supernatants derived from concanavalin A- or phytohemagglutinin-treated cells, but contained more activity than those supernatants derived from lipopolysaccharide-treated cells. CBA spleen cells secreted significantly more LT than Balb/c spleen cells after NaIO 4 stimulation. NaIO 4 -stimulated CBA spleen cells secreted LT in cultures with or without serum, but stimulated Balb/c spleen cells secreted LT only in serum-containing cultures. The advantages of NaIO 4 as an inducer of lymphokines, as opposed to other mitogens or antigens, is the brief exposure of this agent to the cells after which the NaIO 4 is removed, and the lymphokines can be obtained free from the inducer.

Increase in Serum IgE Levels of Ovalbumin-Sensitized Cats and the Detection of Elastase and Collagenase Activities in Secretions of Sensitized Feline Alveolar Macrophages Challenged in vitro

The feline model of respiratory hypersensitivity induced by intraperitoneal injection of ovalbumin has been studied. IgE serum antibodies were present for 3-10 weeks following sensitization, with maximum titers occurring between 50 and 70 days. Similarly, peak passive cutaneous anaphylaxis reactions occurred between 50 and 70 days. Alveolar macrophages, obtained by tracheal lavage at 65 days after sensitization, produced elastase like and collagenase-like secretions 48 h after challenge with ovalbumin in culture. Macrophages from nonsensitized cats did not produce these secretions. It is hypothesized that reaginic antibodies and sensitized alveolar macrophages, such as those found in the cat model, may be responsible in part for the destruction of lung tissue found in long-term respiratory diseases, similar to fibrosing alveolitis and pulmonary emphysema in man.