Effect of C-C chemokine receptor 2 (CCR2) knockout on type-2 (schistosomal antigen-elicited) pulmonary granuloma formation: analysis of cellular recruitment and cytokine responses

Am J Pathol. 1999 May;154(5):1407-16. doi: 10.1016/S0002-9440(10)65394-1.


Monocyte chemotactic protein (MCP)-1 is postulated to play a role in cellular recruitment during inflammatory reactions. C-C chemokine receptor 2 (CCR2) is considered the major G-protein coupled receptor for MCP-1/JE. We reported that mice with knockout of the CCR2 gene display partially impaired type-1 granuloma formation. The present study similarly examined the effect of CCR2 deficiency on synchronously developing type-2 (Th2) cytokine-mediated lung granulomas elicited by embolization of beads coated with Ags of Schistosoma mansoni eggs. Systemically, blood monocytes were reduced by about half throughout the 8-day study period. At the local level, granuloma size and macrophage content were impaired during the early growth phase (days 1 to 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 MCP-5, but reduced IL-4 and IFNgamma mRNA. The latter was possibly related to decreased CD4+ T cell recruitment. Regionally, draining lymph nodes showed panlymphoid hyperplasia with impaired production of IFNgamma, IL-2, and IL-4, but not IL-5, IL-10, or IL-13. Analysis of procollagen gene expression indicated transient impairment of procollagen III transcripts on day 4 of granuloma formation. These findings indicate that agonists of CCR2 contribute to multiple facets of type-2 hypersensitivity granulomatous inflammation.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Helminth / immunology*
  • Cells, Cultured
  • Chemokines / genetics
  • Chemotaxis / physiology
  • Collagen / genetics
  • Cytokines / biosynthesis*
  • Gene Expression
  • Granuloma / genetics*
  • Granuloma / immunology
  • Granuloma / pathology
  • Lung Diseases / genetics*
  • Lung Diseases / immunology
  • Lung Diseases / pathology
  • Lymph Nodes / cytology
  • Lymph Nodes / metabolism
  • Mice
  • Mice, Knockout
  • RNA, Messenger / biosynthesis
  • Receptors, CCR2
  • Receptors, Chemokine / genetics*
  • Schistosoma mansoni / immunology*


  • Antigens, Helminth
  • Ccr2 protein, mouse
  • Chemokines
  • Cytokines
  • RNA, Messenger
  • Receptors, CCR2
  • Receptors, Chemokine
  • Collagen