Splenic macrophages play a key role in regulating cell proliferation during a variety of chronic perturbations of the hematopoietic system. This regulatory activity is in sharp contrast to the activities of inflammatory monocytes/macrophages in that it is not dominated by the secretion of @entity2918 or toxic metabolites such as @entity2627 . A productive model for studying these nontoxic regulatory activities of splenic macrophages has been provided by macrophages generated in vitro (M phi-c) during autologous spleen cell culture. The M phi-c effectively inhibit (greater than 90%) lymphocyte proliferation by inhibiting G1----S phase progression without inhibiting the production of interleukins by the lymphocytes. Conditioned medium from M phi-c activated with @entity558 + @entity3692 effected a similar @entity1167 of activated lymphocytes. The involvement of @entity2391 in effecting the antiproliferative activity is suggested by (1) the ability of monospecific anti- @entity2391 mAB, but not anti- @entity2533 , anti-IL-1, anti- @entity310 , or anti- @entity379 , to neutralize the antiproliferative activity in the M phi-c supernatants and (2) the ability of purified @entity2391 to effect a similar inhibition of cell proliferation (i.e., @entity1167 without inhibition of interleukin production). @entity1505 and @entity3692 could not effect such an inhibition of cell proliferation and did not synergize with @entity2391 in producing such an antiproliferative effect. The M phi-c could be activated to effector function by a combination of @entity558 + @entity3692 or @entity1505 + @entity3692 , but not by any one of those reagents alone. @entity558 alone was sufficient to stimulate @entity310 production by the M phi-c. Activation of the M phi-c by @entity558 + @entity3692 could be completely blocked by anti- @entity310 antibodies. These data suggest that the M phi-c can be induced to produce inhibitory levels of cytostatic cytokines by a @entity310 autocrine loop that is @entity379 dependent. The in vivo relevance of this effector mechanism is suggested by, and discussed in the context of, the recent reports of "spontaneous" production of @entity2391 during immunological disorders.

Evidence for involvement of XXXX in the induction phase and @entity2391 in the effector phase of antiproliferative activity of splenic macrophages.

@entity558 :: ('MESH:C536528', 'Disease') :: ['LPS'] @entity2627 :: ('MESH:D010545', 'Chemical') :: ['peroxides'] @entity3692 :: ('25712(Tax:10116)', 'Gene') :: ['rIFN-gamma'] @entity310 :: ('7124', 'Gene') :: ['TNF-alpha'] @entity1505 :: ('24835(Tax:10116)', 'Gene') :: ['rTNF-alpha'] @entity2918 :: ('MESH:D011453', 'Chemical') :: ['prostaglandins'] @entity2533 :: ('7040', 'Gene') :: ['TGF-beta'] @entity379 :: ('3458', 'Gene') :: ['IFN-gamma'] @entity2391 :: ('3456', 'Gene') :: ['IFN-beta'] @entity1167 :: ('MESH:D006323', 'Disease') :: ['G1 arrest']
@entity310 :: (7124,Gene) :: ['TNF-alpha']
