Role of beta 2 integrins in the recruitment of phagocytic cells in joint inflammation in the rat.
Adhesion molecules of the beta 2 family of integrins play an important role in adhesion and migration of leukocytes to inflammatory sites. Several in vivo studies indicate that not only monoclonal antibodies (mAbs) directed against the common beta subunit (CD18) but also to the individual alpha subunits (CD11a, CD11b) can effectively inhibit different types of inflammation. In this study we report that in the adjuvant arthritis (AA) alpha CD11a, alpha CD11b, or even alpha CD18 treatment could not prevent disease development. Moreover, we examined the same mAbs in an acute nonspecific inflammation at different sites in the rat. We found that pretreatment with alpha CD11a or alpha CD11b could significantly block a zymosan peritonitis, but appeared to have no effect on a locally induced joint or dermal inflammation. Interestingly, alpha CD18 treatment, which blocks the entire CD11/CD18 complex, was able to inhibit the influx of inflammatory cells in a peritonitis as well as in a joint and dermal inflammation. These data not only indicate that the type of joint inflammation determines which adhesion molecules play a role in transendothelial migration, but also that involvement of the beta 2 integrins is highly site specific.
van de Langerijt
A G
AG
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
Huitinga
I
I
Joosten
L A
LA
Dijkstra
C D
CD
Van Lent
P L
PL
van den Berg
W B
WB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000276:immunology* / Q000628:therapy; D005260:Female; D016023:Integrins / Q000502:physiology*; D008297:Male; D010538:Peritonitis / Q000139:chemically induced / Q000628:therapy; D010586:Phagocytes / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D015054:Zymosan
D000911:Antibodies, Monoclonal; D016023:Integrins; D015054:Zymosan