LYMPHOCYTES MEDIATE TNF-ALPHA-INDUCED ENDOTHELIAL-CELL ADHESION MOLECULE EXPRESSION - STUDIES ON SCID AND RAG-1 MUTANT MICE

TNF-alpha is known to elicit a rapid increase in the expression of spe cific endothelial cell adhesion molecules (ECAMs) within different vas cular beds. The aim of this study was to determine whether lymphocytes contribute to the increased ECAM expression elicited by TNF-alpha. A dual radiolabeled mAb technique was used to quantify constitutive and TNF-alpha-induced expression of ICAM-1, VCAM-1, E-selectin, and P-sele ctin in different vascular beds (lung, heart, stomach, mesentery, smal l intestine, large intestine, and muscle) in wild-type and SCID mice. In reconstitution experiments, either whole splenocytes, T cell-enrich ed splenocytes, or B cell-enriched splenocytes were injected into SCID mice 48 h before TNF-alpha administration. Although the constitutive expression of ECAMs differed only slightly between wild-type and SCID mice, TNF-alpha-induced ECAM expression was markedly blunted in SCID m ice compared with wild-type mice. This blunted response to TNF-alpha w as also demonstrated for VCAM-1 in recombination activating gene (RAG) -1 mutant mice. Reconstitution studies revealed that administration of 50 x 10(6) splenocytes in SCID mice at 48 h before cytokine treatment restored the TNF-alpha-induced expression of VCAM-1 to levels normall y observed in wild-type mice. Reconstitution with T cell- but not B ce ll-enriched splenocytes, also restored the TNF alpha-induced expressio n of VCAM-1 in SCID mice to wild-type levels, These results implicate circulating T lymphocytes as modulators of the increased ECAM expressi on elicited by TNF-alpha.