Katsunori Sugisaki

Rabbit vascular endothelial adhesion molecules: ELAM-1 is most elevated in acute inflammation, whereas VCAM-1 and ICAM-1 predominate in chronic inflammation

Activation of the microvasculature is a major component of the inflammatory response. During inflammation the vascular endothelium not only becomes more permeable to plasma proteins but also develops adhesion molecules that initiate the local immigration of leukocytes. We describe herein the in vivo changes in the three major vascular adhesion molecules during the development and healing of two types of rabbit dermal inflammatory lesions: (1) acute lesions produced in rabbits by the topical application of 1% sulfur mustard (SM, the military irritant/toxicant); and (2) chronic (immune‐mediated) lesions produced in rabbits by intradermal injections of Mycobacterium bovis (BCG), the vaccine strain of tubercle bacillus. In each case, frozen tissue sections were made from lesions of various ages and stained immunohistochemically for von Willebrand (vW) factor to measure the total functional microvasculature. The sections were also stained immunohistochemically for the vascular endothelial adhesion molecules ICAM‐1, ELAM‐1 (E‐selectin), and VCAM‐1, and for the leukocyte ligands for ICAM‐1: LFA‐1 (CDlla/CD18) and Mac‐1 (CD11b/CD18). Infiltrating monocytes and lymphocytes expressed the LFA‐1 ligand and infiltrating PMN expressed the MAC‐1 ligand. The area of stained microvasculature per square millimeter of tissue section was determined with the use of a computerized image analyzer. Edema and cell infiltration spread apart the microvessels, changing the number of microvessels per square millimeter of tissue section. Three methods of assessing such changes are presented. In SM lesions, endothelial ICAM levels were decreased from normal by about 50% at 1 and 2 days (when the lesions reached their peak size) and returned to normal at 3 and 6 days (during the healing process). ELAM rose in peak SM lesions and remained high during healing. VCAM levels, however, were only elevated in the 6‐day (almost healed) lesions. In BCG lesions the levels of endothelial ICAM and VCAM (and to a lesser extent ELAM) were increased at 9 days and remained so as the size of the lesions peaked at 23 days. During the healing phase at 37 days, the elevated ICAM and VCAM levels decreased but the slightly increased ELAM levels persisted. These findings indicate that ELAM plays a major role in acute inflammation and that VCAM and ICAM play major roles in chronic inflammation. VCAM is known to be monocyte and lymphocyte selective. J. Leukoc. Biol. 60: 692–703; 1996.

Links between bronchial asthma and allergic rhinitis in the Oita Prefecture, Japan.

Recent studies have strengthened the concept that bronchial asthma and allergic rhinitis are manifestations of an inflammatory process within a continuous airway. This study was performed to compare clinical findings in asthma with or without rhinitis in Japan. Nasal symptoms were present in 99.6% of asthma patients. The prevalence of allergic rhinitis in patients with asthma was 52.4%. Bronchial asthma attacks in one third of patients with rhinitis were coincident with worsening of nasal symptoms. In adults (> 16 years of age), rhinitis frequently preceded asthma, whereas asthma preceded rhinitis in children (< 16 years of age). The frequency of rhinitis in asthma decreases with increasing age. This study demonstrated a clear link between upper and lower airway disorders in Japan.

NONSPECIFIC AND IMMUNE-SPECIFIC UP-REGULATION OF CYTOKINES IN RABBIT DERMAL TUBERCULOUS (BCG) LESIONS

To our knowledge, this is the first sequential study of cytokines in tissue sections of developing and healing tuberculous (BCG) lesions. In situ hybridization, immunohistochemical, and RT‐PCR techniques were used. Cytokine mRNAs showed a biphasic pattern. The percentage of mononuclear cells (MN) containing IL‐1β, TNF‐α, MCP‐1, and IL‐8 mRNAs was highest in 1‐ to 3‐day lesions, apparently because of the nonspecific inflammatory response caused by the tubercle bacilli in the BCG vaccine. At 5 days, this percentage was significantly reduced. With IFN‐γ, the peak and trough were delayed by 2 days. By 9 days, the percentage of MN containing the mRNAs of all five cytokines had again increased and the rabbits had become tuberculin‐positive. In general, MCP‐1 and TNF‐α proteins and the vascular adhesion molecules, ICAM, VCAM, and perhaps ELAM, peaked at about 3 days. Many mononuclear cells surrounding the central areas of solid and liquefied caseous necrosis contained chemokine IL‐8 mRNA. IL‐8 is known to attract PMN, and PMN were present nearby. In contrast, MN containing chemokine MCP‐1 mRNA were present more peripherally in areas rich in macrophages and lymphocytes. The early nonspecific cytokine response seems to be an adjuvant effect of the mycobacteria in BCG vaccine in that it causes a rapid entry of macrophages, lymphocytes, granulocytes, and probably dendritic cells into local sites of antigen deposition. This effect should be considered in developing improved vaccines for the prevention of tuberculosis, because BCG vaccines producing a strong early cytokine response should be more immunogenic than BCG vaccines with similar antigens producing a weak response. J. Leukoc. Biol. 63: 440–450; 1998.

A Case of Malignant Hemangiopericytoma: An Immunohistochemical and Ultrastructural Study

We report one case of malignant hemangiopericytoma which started with a tumor in the lower jaw and multiple nodules in the lung. The tumor quickly metastasized to the brain and chemotherapy was not at all effective. Hemangiopericytoma is generally diagnosed by its histological characteristics. Recently, however, electron microscopy and immunohistochemical methods have been used for its diagnosis. In our case, electron micrograph showed the growth of hemangiopericytoma cells around immature endothelial cells. In addition, the tumor cells reacted positively only with anti-vimentin antibodies, and the endothelial cells in the tumor tissue were positive for antifactor VIII antibodies. The observed features were consistent with the characteristics of hemangiopericytoma.

α-Naphthyl Acetate Esterase-1 (ANAE-1) Secreted by Epithelioid Cells from Induced Rabbit Lung Granuloma Showed MIF Activity

The function of alpha-naphthyl acetate esterase-1, whose isoelectric point values range from 5.15 to 5.45, was examined. A higher value of alpha-naphthyl acetate esterase-1 was detected in the extracts of epithelioid cells isolated from rabbit lung granuloma at 4 weeks after injection of Freunds complete adjuvant, compared to those values of alveolar macrophages isolated from the same lungs described above and of the normal lungs. Additionally, this enzyme activity was observed to be prominent in the culture supernatants of epithelioid cells. alpha-Naphthyl acetate esterase-1 was purified from lung granuloma as a single 62-kDa band by SDS-PAGE analysis. The purified enzyme showed a macrophage migration inhibition activity at concentrations over 20 nM, and its activity was dose-dependent. Moreover, when various amounts of the purified enzyme were added to lymphocyte-derived macrophage migration inhibitory factor, macrophage migration inhibition was significantly enhanced with a dose-dependent manner. The results suggest that alpha-naphthyl acetate esterase-1 secreted by granuloma macrophages, particularly by epithelioid cells, contributes to granuloma formation.