Biodefense function of omental milky spots through cell adhesion molecules and leukocyte proliferation

Abstract

To evaluate the immunological functions of the greater omentum in the peritoneal cavity, the localization of cell adhesion molecules (CAMs) on mesothelial cells and leukocytes in the omental milky spots were studied in normal and lipopolysaccharide (LPS)-stimulated mice by means of immunoelectron microscopy. The milky spots featured numerous leukocytes among the dome-shaped mesothelial cells, even in the normal stable state. Leukocyte integrins LFA-1, Mac-1, and VLA-4 were preferentially localized to microvilli and ruffles of macrophages and lymphocytes. The mesothelial cells of the milky spots showed higher ICAM-1 levels than did those of other omental regions, and fibronectin was detected in the stomata. The number of leukocytes markedly increased following an increase in proliferating cell nuclear antigen (PCNA)-positive cells in the milky spots after LPS stimulation. The mesothelial cells contained VCAM-1 newly restricted to the microvilli and increasing amounts of ICAM-1. These results show that the omental milky spots are active sites for leukocyte migration and peritoneal leukocyte supply because of the presence of adhesion molecules and active cell proliferation. Proliferative active leukocytes and those that have migrated from vessels pass through the stomata via an interaction of VLA-4 and fibronectin, adhere to the microvilli of the activated mesothelial cell surface as the result of an interaction between ICAM-1/VCAM-1 and integrins, and exude into the peritoneal cavity. Much of the exudation and adhesion of leukocytes seen in the milky spots of LPS-stimulated mice may be attributable to an increase in cell proliferation and in the amounts of ICAM-1 and VCAM-1.

A comparative study of local defense spots within the peritoneal cavity in Japanese quails,Coturnix coturnix japonica(Galliformes, Phasianidae) and Wistar rats,Rattus norvegicus(Rodentia, Muridae)

“…The presence of T, B lymphocytes, predominantly macrophages, and mast cells in the milky spots were reported in rats (Takemori & Ito 1981;Cranshaw & Leak 1990;Krist et al 1995;Van Vugt et al 1996;Di Paolo & Sacchi 2000;Cui et al 2002). Evidence gathered in the present study is in agreement with these observations and further demonstrates the presence of lymphocyte, macrophage, plasma cells and mast cells in the quail.…”

Mechanisms of peritoneal dissemination in gastric cancer (Review)

“…There are numerous reasons for this paradox, besides the stomata exposing the submesothelial tissue to the cancer cells. Firstly, the levels of cellular adhesion molecules, including intercellular adhesion molecule 1, of the mesothelial cells that are on the surface of milky spots are increased compared with in other peritoneal regions, which may promote cell adhesion (77). Secondly, Oosterling et al (76) observed that the milky spots are insufficient to prevent peritoneal dissemination even in minimal residual disease, suggesting that an omentectomy may be required to prevent peritoneal dissemination for certain intra-abdominal malignancies.…”

Preferential Attachment of Peritoneal Tumor Metastases to Omental Immune Aggregates and Possible Role of a Unique Vascular Microenvironment in Metastatic Survival and Growth

“…[42][43][44] When analyzed for intracellular VEGF-A, 25 Ϯ 1.3% of the mesothelial cells demonstrated a 6.4-fold increase over controls under normoxic conditions ( Figure 5C). Hypoxia increased this population to 39 Ϯ 3.9% and further induced VEGF-A production to 10-fold greater than controls (P Ͻ 0.…”