INVOLVEMENT OF GRANULOCYTES AND THE ADHESION RECEPTORS INTERCELLULAR-ADHESION MOLECULE-1 AND LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 IN TISSUE INFLAMMATION-INDUCED BY TH2-TYPE HELPER-CELLS
Km. Muller et al., INVOLVEMENT OF GRANULOCYTES AND THE ADHESION RECEPTORS INTERCELLULAR-ADHESION MOLECULE-1 AND LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 IN TISSUE INFLAMMATION-INDUCED BY TH2-TYPE HELPER-CELLS, Journal of investigative dermatology, 104(3), 1995, pp. 350-354
We reported recently that subcutaneously injected, anti-CD3 epsilon-pu
lsed polyclonal Th2 cells mediate interleukin-4-dependent local tissue
inflammation. Because a prominent polymorphonuclear infiltrate was ob
served in the lesions at the time of maximal tissue swelling, we inves
tigated the involvement of polymorphonuclear leukocytes and their adhe
sion molecules lymphocyte function-associated antigen-1 (LFA-1) and in
tercellular adhesion molecule-1 (ICAM-1) in Th2-cell-mediated inflamma
tion. Pretreatment of recipient mice with a depleting monoclonal antib
ody to neutrophils or with blocking antibodies to LFA-1 or to ICAM-1 c
ompletely abrogated tissue swelling in Th2-cell-mediated inflammation.
Granulocyte infiltration at 6 h was also inhibited by the antibodies
to neutrophils and to ICAM-1, but not by that to LFA-1, Tissue swellin
g mediated by Th1 cells had different kinetics and was not prevented b
y administration of anti-neutrophil antibody: maximal edema formation
occurred at: 24-48 h, when the predominant cellular infiltrate was mon
onuclear. Because the Th1-cell-induced infiltrate at 6 h also consiste
d of granulocytes but was not associated with pronounced edema, the me
re presence of infiltrating polymorphonuclear leukocytes seems not to
be sufficient to induce edema, Because edema but not granulocyte infil
tration was inhibited by anti-LFA-1 and because anti-LFA-1 antibodies
are known to inhibit several functions of neutrophils, our results sug
gest that, in inflammation mediated by Th2 cells, granulocytes induce
edema through their activation and/or degranulation.