Effect of C-C chemokine receptor 2 (CCR2) knockout on type-2 (schistosomalantigen-elicited) pulmonary granuloma formation - Analysis of cellular recruitment and cytokine responses

Monocyte chemotactic protein (MCP)-1 is postulated to play a role in cellul ar recruitment during inflammatory reactions. C-C chemokine receptor 2 (CCR 2) is considered the major G-protein coupled receptor for MCP-1/JE, We repo rted that mice with knockout of the CCR2 gene display partially impaired ty pe-1 granuloma formation, The present study similarly examined the effect o f CCR2 deficiency on synchronously developing type-2 (Th2) cytokine-mediate d lung granulomas elicited by embolization of beads coated with Ags of Schi stosoma mansoni eggs. Systemically, blood monocytes were reduced by about h alf throughout the g-day study period. At the local level, granuloma size a nd macrophage content were impaired during the early growth phase (days 1 t o 2), By day 4, granuloma sizes were similar to controls. In granulomatous lungs, CCR2 knockout increased mRNA for CCR2 agonists, MCP-1, MCP-3, and MC P-5, but reduced IL-4 and IFN gamma mRNA. The latter was possibly related t o decreased CD4+ T cell recruitment. Regionally, draining lymph nodes showe d panlymphoid hyperplasia with impaired production of IFN gamma, IL-2, and IL-4, but not IL-5, IL-10, or IL-13, Analysis of procollagen gene expressio n indicated transient impairment of procollagen III transcripts on day 4 of granuloma formation. These findings indicate that agonists of CCR2 contrib ute to multiple facets of type-2 hypersensitivity granulomatous inflammatio n.