In vivo roles of integrins during leukocyte development and traffic: Insights from the analysis of mice chimeric for alpha(5), alpha(v), and alpha(4)integrins

Mice chimeric for integrins alpha(5), alpha(V), or alpha(4) were used to di ssect the in vivo roles of these adhesion receptors during leukocyte develo pment and traffic. No major defects were observed in the development of lym phocytes, monocytes, or granulocytes or in the traffic of lymphocytes to di fferent lymphoid organs in the absence of alpha(5) or alpha(V) integrins, H owever, in agreement with previous reports, the absence of alpha(4) integri ns produced major defects in development of lymphoid and myeloid lineages a nd a specific defect in homing of lymphocytes to Peyer's patches. In contra st, the cr,integrin subunit is not essential for localization of T lymphocy tes into intraepithelial and lamina propria compartments in the gut, wherea s one of the partners of alpha(4), the beta(7) chain, has been shown to be essential. However, alpha(4)-deficient T lymphocytes cannot migrate properl y during the inflammatory response induced by thioglycolate injection into the peritoneum, Finally, in vitro proliferation and activation of lymphocyt es deficient for alpha(5), alpha(V), or alpha(4) integrins' upon stimulatio n with different stimuli were similar to those seen in controls, These resu lts show that integrins play distinct roles during in vivo leukocyte develo pment and traffic.