Raymond D.A. Peterson

Monoclonal antibody identification of a type II alveolar epithelial cell antigen and expression of the antigen during lung development

A monoclonal antibody identifying an antigen expressed by rat type II alveolar epithelial cells, but not by type I epithelial cells or other mature lung cells, was produced by immunization of mice with cells of the rat L2 cell line. The antigen recognized by the antibody was present on the microvillous luminal surface of type II epithelial cells. In adult rat lung, only type II epithelial cells bound the antibody. During fetal development the antigen was expressed by cuboidal epithelial cells lining the respiratory ducts of the first divisions of the tracheal bud, but not by epithelial cells lining the esophagus or trachea. The antigen continued to be expressed by cuboidal epithelial cells lining the larger respiratory ducts until approximately 19 days gestational age. Thereafter, expression was increasingly limited to selected single cells or clusters of two to four cuboidal cells in the smallest ducts. By the 21st postnatal day, the antigen was expressed only by type II alveolar epithelial cells. Type II alveolar epithelial cells isolated from adult lung and the L2 cell line in culture expressed the antigen on the cell surface. A protein of approximately 146,000 Mr was isolated by immunoadsorption of the antigen from non-ionic detergent extracts of type II cells and L2 cells. Preliminary studies of the binding of the antibody to other rat tissues indicate that the antibody binds to renal proximal tubular epithelial cells of the kidney and the luminal surface of the small bowel epithelial cells.

In vitro lymphocyte activity in women with endometriosis—an altered immune response? * †

OBJECTIVE To determine the possible role of the immune system in the pathogenesis of endometriosis. DESIGN The lymphocyte proliferative response in the presence of autologous endometrial cells was assayed by tritiated thymidine incorporation. SETTING Patients were recruited from a university outpatient clinic. MAIN OUTCOME MEASURE To determine the lymphocyte proliferative response to endometrium in controls and patients with endometriosis. PARTICIPANTS Twenty patients with endometriosis and 26 control women were studied. RESULTS The lymphocyte proliferative response in the presence of autologous endometrium was significantly lower in women with endometriosis when compared with controls. CONCLUSION This study indicates that an altered lymphocyte/endometrial cell relationship is operational in women with endometriosis and may contribute to the pathogenesis of the disease.

An organ culture system for study of fetal lung development.

Abstract Fetal rat lungs placed in in vitro organ culture at 15.5 days gestation grow significantly based on accumulation of DNA and protein. In the experimental system described, DNA accumulated rapidly during the first three days in culture and increased from 4.8 to 15.6 micrograms per lung culture. Protein content increased more slowly and reached a value more than double the initial value after six days in the culture system. Glycogen accumulated in the tissue during the first six days in culture and was depleted during the subsequent culture period, a pattern strikingly similar to that observed during lung development in vivo . Phospholipid accumulation was biphasic with respect to time with an inflection point at about the sixth day of culture. The phosphatidylcholine species synthesized in the culture system in vitro were similar to those produced in vivo in fetal lung at 21 days gestation.

Speculations on ataxia-telangiectasia: defective regulation of the immunoglobulin gene superfamily

In this short article, Raymond Peterson and Jane Funkhouser develop the argument that the common molecular mechanism linking the various clinical manifestations of ataxia-telangiectasia (AT) is a defect in the regulation of the immunoglobulin (Ig) gene superfamily. They propose that the AT gene codes for a protein essential for the orderly expression of this gene family, perhaps regulating the gene rearrangement process that appears to be a unique characteristic of this system. Members of the Ig gene superfamily play a major role in the development and operation of the immune and nervous systems, and any perturbation of their expression would be anticipated to produce a panoply of signs and symptoms, such as those characterizing the AT phenotype.

Association Between Maternal‐Fetal HLA‐DR Relationships and Fetal Growth

PROBLEM: To determine whether maternal‐fetal human leukocyte antigen (HLA) antigenic relationships are associated with differential fetal growth in weight.

Regulation of expression of aminopeptidase N in fetal rat lung by dexamethasone and epidermal growth factor

Aminopeptidase N (EC 3.4.11.2) (APN) is an ectopeptidase expressed in lung at the apical surface of alveolar type II epithelial cells. Its expression is up-regulated during fetal lung development. Recently several ectopeptidases have been recognized as possible regulators of growth and cell differentiation through their role in hydrolysis of autocrine and paracrine peptides that influence these processes. The studies reported here describe effects of factors known to promote lung development and differentiation of the alveolar epithelium on expression of aminopeptidase N during fetal lung development in organ culture. Fetal rat lung was placed in organ culture at the 15th gestational day and cultured for 6 days in the presence or absence of the synthetic glucocorticoid hormone dexamethasone or epidermal growth factor (EGF). Steady-state levels of APN mRNA increased approximately 10-fold during the 6-day culture. During this time the lung alveolar epithelium developed to the point where immature alveolar type II cells were recognized by the presence of lamellar bodies. Dexamethasone or EGF increased the levels of APN mRNA in the fetal lung 2-to 3-fold over control cultures by the third day in culture and concurrently accelerated the morphological development of the alveolar epithelium. Differences in treated and control cultures diminished after 6 days in culture when the epithelium appeared more mature, suggesting that the immature epithelium was more responsive to the treatments.

Does exposure to HLA alloantigens trigger immunoregulatory mechanisms operative in both pregnancy and aids

The complex biological processes responsible for regulating the immune system are presently the subject of considerable interest and study. New insight into this process comes from a variety of observations and it is the purpose of this communication to develop the hypothesis that two seemingly quite disparate observations point to a common biological mechanism bearing on immunoregulation. The observations concern the unique immunologic relationship between mother and fetus and the immunoregulatory abnormalities encountered in HIV-induced acquired immunodeficiency syndrome (AIDS). Exposure to foreign (allo) major histocompatibility complex (MHC) antigens can potentially occur during pregnancy, the transfusion of blood or blood products, or anal insemination. The hypothesis, in its simplest form, states that such MHC alloantigenic exposure triggers a sequence of immunoregulatory mechanisms resulting in immunosuppression and that this response has evolved in placental mammals as a means of protecting the fetus from maternal immune rejection and promoting optimal fetal development.

Pathogenesis of an experimental meningeal leukemia model

Abstract Syngeneic mice injected intravenously with a T-cell tumor line developed widespread bone marrow and visceral leukemic infiltration 10 days after inoculation. This was followed by a sequence of focal and then diffuse tumoral infiltration of the cranial duramater, subdural space, and leptomeninges. The involvement of the duramater was shown to result from direct local extension of leukemic cells from the cranial bone marrow along the adventitia of blood vessels. The leptomeningeal infiltration that followed occurred via the adventitia of veins connecting the duramater with the arachnoid. This mechanism of direct spread of marrow leukemic cells into the meninges has been shown to occur in other experimental models and has been suggested in some human autopsy studies of meningeal leukemia. It is postulated that this pathogenetic mechanism may operate in some instances of the human disease, instead of the more commonly accepted hematogenous spread of meningeal leukemia.

Regulators of Iron Absorption in the Small Intestine

The absorption of iron can not be explained solely by transferrin and iron. Therefore, a search was undertaken to discover other iron binding proteins in homogenates of rat duodenum. Using heat, ammonium sulfate precipitation, serial chromatography and immunologic methods, we have identified four iron binding substances which are both biologically and immunologically distinct from ferritin and transferrin. Two of these iron binding complexes are water soluble with molecular sizes of about 520,000 and 60,000 daltons respectively. One of the water insoluble proteins is soluble in triton X-100 and is probably a membrane protein with a molecular size of about 60,000 daltons. Insoluble mucin is believed to be the fourth newly identified iron binding complex.

Lymphocyte alloantigenic challenge as a potential cofactor in HIV infection and progression to AIDS

A hypothesis is developed that circulatory exposure to alloantigens found on lymphocytes triggers a series of events leading to suppression of the cell‐mediated arm of the immune system and, therefore, that such alloantigenic challenge can be an important cofactor promoting infection with the human immunodeficiency virus (HIV) and development of the acquired immunodeficiency syndrome (AIDS) following infection. The explanatory model that is developed is based in large part on current knowledge of the results of fetal lymphocyte alloantigenic challenge of the maternal immune system. It is our contention that the maternal response which leads to suppression of cell‐mediated immunity is a mechanism promoting survival of the fetal “allograft,” and that this mechanism is an evolutionary adaptation in humans and other placental mammals. We also hypothesize that circulatory exposure to these same alloantigens leads to an immunosuppressive state which enhances survival of HIV in an exposed individual and augments the immunosuppressive action of HIV in promoting progression to clinical AIDS. Findings from studies of individuals who are at risk for exposure to lymphocyte alloantigenic challenge and from HIV infected patients are reviewed and discussed in light of this hypothesis.