Molecular mechanisms to form leukocyte infiltration patterns distinct between synovial tissue and fluid of rheumatoid...

There is a striking difference in the leukocyte infiltration pattern between synovial tissue and fluid of rheumatoid arthritis, a monocyte/macrophage-predominant infiltration in the former and a polymorphonuclear leukocyte (PMN)-predominant one in the latter. In extracts of rheumatoid arthritis synovial tissue, there is a strong chemotactic activity to monocytes but a negligible one to PMNs. The monocyte-specific chemotactic factor in the extracts represents dimers (and oligomers) of the S19 ribosomal protein which are cross-linked by a transglutaminase-catalyzed reaction. This oligomer formation may correlate to apoptosis in the lesion. On the other hand, in the synovial fluids there is the co-presence of chemotactic factors effective on PMNs as well as on monocytes and a strong chemotaxis inhibitor specific to monocytes. This inhibitory molecule is C4a which is liberated from complement component 4 in the presence of immune complexes. C4a exhibits its inhibitory activity indirectly by stimulating monocytes to release an autocrine or paracrine inhibitory cytokine to monocyte chemotaxis. These molecular mechanisms seem at least partly to cause the two distinct patterns of leukocyte infiltration in rheumatoid arthritis.