Activation of alveolar macrophage TNF and MCP-1 expression in vivo by a synthetic peptide of C-reactive protein.
Administration of multilamellar vesicles (MLV) encapsulating a synthetic peptide (RS-83277) derived from human C-reactive protein (CRP) augments anti-tumor activity of murine alveolar macrophages and reduces established pulmonary metastases of experimental tumors. To explore mechanisms involved in these phenomena, we investigated cytokine and integrin (CDllb) expression of bronchoalveolar lavage (BAL)-derived alveolar macrophages in control (blank MLV) and RS-83277-MLV-treated C57BI mice. Alveolar macrophage production of tumor necrosis factor alpha (TNF-alpha) and monocyte chemoattractant bioactivity increased at 48 h after treatment with RS-83277-MLV but not control MLV. Chemoattractant activity was neutralized by antibody to monocyte chemoattractant protein-1 (MCP-1), but not irrelevant immunoglobulin G(IgG). Changes were reflected by augmented TNF-alpha and MCP-1 mRNA levels in pulmonary tissue and enhanced CD11b expression on mononuclear leukocytes derived from total lung tissue, but not on BAL-derived alveolar macrophages. Results suggest that RS-83277-MLV treatment is associated with activation of alveolar macrophage TNF-alpha and MCP-1 production and up-regulation of adhesion molecules on pulmonary mononuclear leukocytes but not on alveolar macrophages.
Barna
B P
BP
Department of Clinical Pathology, Cleveland Clinic Foundation, Ohio, USA.
Thomassen
M J
MJ
Zhou
P
P
Pettay
J
J
Singh-Burgess
S
S
Deodhar
S D
SD
D000595:Amino Acid Sequence; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002097:C-Reactive Protein / Q000737:chemistry / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000378:metabolism*; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression; D007155:Immunologic Factors / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D007155:Immunologic Factors; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010455:Peptides; D012333:RNA, Messenger; C079718:RS 83277; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein