T-CELL AND B-CELL INDEPENDENCE OF ENDOTHELIAL-CELL ADHESION MOLECULE EXPRESSION IN PULMONARY GRANULOMATOUS INFLAMMATION

A pulmonary Cryptococcus neoformans (Cne: strain 52D, ATCC24067) infec tion model in mice was used to examine the possible role for T cell-me diated immunity in regulating vascular adhesion molecules on lung endo thelium during development of granulomatous inflammation. Resolution o f pulmonary Cne infection in C.B-17 mice begins by Day 14 following in tratracheal inoculation and depends on T cell-mediated recruitment of monocytes followed by their activation. C.B-17 scid/scid (SCID) mice m ount a less exuberant pulmonary inflammatory response, recruit fewer m onocytes into their lungs, and fail to clear the infection. Recruitmen t of leukocytes into infected tissue is mediated by both the interacti on of adhesion molecules expressed on the surface of activated vascula r endothelial cells with ligands on circulating cells, and the directe d response of these leukocytes to chemotactic factors. The kinetics of expression of the endothelial cell adhesion molecules E-selectin, vas cular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion mol ecule-1 (ICAM-1), all previously shown to regulate monocyte recruitmen t, were examined in the lungs of infected C.B-17 and SCID mice during pulmonary infection to determine if T cells were necessary for their u pregulation. Immunohistochemical analysis showed that upregulation of E-selectin, VCAM-1, and ICAM-1 did not differ significantly between C. B-17 and SCID mice at any time during infection. Maximal expression in C.B-17 and SCID mice was noted between Days 5 and 7 for all three mol ecules and preceded maximal influx of leukocytes into the lung. Thus, the inability of SCID mice to recruit optimal numbers of monocytes int o infected lungs was not the result of a failure to express the critic al adhesion molecules early in infection, but likely reflected absence of immune dependent chemotactic factors.