Role of monocyte chemoattractant protein-1 (MCP-1) in Th1 (mycobacterial) and Th2 (schistosomal) antigen-induced granuloma formation: relationship to local inflammation, Th cell expression, and IL-12 production.
The present study examined the contribution of monocyte chemotactic protein-1 (MCP-1) to granulomatous inflammation mediated by Th1- and Th2-related cytokines. Types 1 and 2 lung granulomas (GR) were respectively induced in presensitized CBA mice by embolization of beads coupled to purified protein derivative of Mycobacteria tuberculosis or soluble Ags derived from Schistosoma mansoni eggs. MCP-1 was spontaneously produced by intact GR, isolated GR macrophages, and draining lymph node cultures, but levels were greater in the type 2 than in the type 1 response. In vivo depletion of IFN-gamma augmented type 2 inflammation and local MCP production; IL-4 depletion had the opposite effect. These treatments had no significant effect on the type 1 response. Treatment with anti-MCP-1, but not that with anti-MIP-1alpha, Abs caused a 30% decrease in type 2 GR area. Neither treatment affected the type 1 GR. Intrinsic MCP-1 was detected immunohistochemically within lymph nodes and appeared to support IL-4-/IL-5-producing lymph node cells. In addition, MCP-1 inhibited IL-12 production by inflammatory macrophages. The latter was demonstrated as a potentially direct effect of MCP-1 on macrophages. These findings show that MCP-1 contributes more to type 2 than to type 1 cytokine-mediated inflammation and suggest a broader role for chemokines in regulating Th cell expression.
Chensue
S W
SW
Department of Pathology, Veterans Affairs Medical Center, Ann Arbor, MI 48105, USA.
Warmington
K S
KS
Ruth
J H
JH
Sanghi
P S
PS
Lincoln
P
P
Kunkel
S L
SL
D000818:Animals; D000942:Antigens, Bacterial / Q000502:physiology*; D000947:Antigens, Helminth / Q000502:physiology*; D018932:Chemokine CCL2 / Q000502:physiology*; D005260:Female; D006099:Granuloma / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D009161:Mycobacterium / Q000276:immunology*; D012547:Schistosoma / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
D000942:Antigens, Bacterial; D000947:Antigens, Helminth; D018932:Chemokine CCL2; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma