N Ahmed, R Thorley, D Xia, D Samols and RO Webster
Department of Internal Medicine, St. Louis University School of Medicine, Missouri, USA.

The acute phase protein, C-reactive protein (CRP), can increase more than a thousandfold during acute inflammatory states, and it is known to modulate neutrophil-mediated inflammatory responses. We have previously shown that CRP inhibits chemotaxis of C5a-stimulated neutrophils in vitro and that rabbits with elevated CRP blood levels exhibit diminished pulmonary vascular permeability and neutrophil infiltration in a model of alveolitis. To study the effect of CRP on alveolitis induced by different chemoattractants, transgenic mice capable of expressing rabbit CRP in a dietary-inducible fashion were treated with inflammatory doses of the chemoattractants. Intratracheal installation of FMLP (8 x 10(-10) mol), LTB4 (2 x 10(-11) mol), or IL-8 (5 x 10(-12) mol) in normal CF1 mice resulted in significant (p<0.05) influx of neutrophils and protein into the alveolar space. Transgenic mice with elevated plasma levels of CRP showed significantly (p<0.05) diminished infiltration of neutrophils into bronchoalveolar lavage fluid (BALF) and significant reduction in BALF protein compared with that in normal mice. Rabbit CRP (10 to 500 micrograms/ml) inhibited in vitro neutrophil chemotaxis in a concentration-dependent fashion when stimulated by the various chemoattractants examined. These data show that rabbit CRP can modify both in vivo and in vitro neutrophil responses to several classes of chemoattractants and that CRP has a significant protective effect in alveolitis by reducing neutrophil influx and protein leakage into the lung.

This article has been cited by other articles:

				W. Rodriguez, C. Mold, M. Kataranovski, J. A. Hutt, L. L. Marnell, J. S. Verbeek, and T. W. Du Clos C-Reactive Protein-Mediated Suppression of Nephrotoxic Nephritis: Role of Macrophages, Complement, and Fc{gamma} Receptors J. Immunol., January 1, 2007; 178(1): 530 - 538. [Abstract] [Full Text] [PDF]

				W. Pitiphat, M. W. Gillman, K. J. Joshipura, P. L. Williams, C. W. Douglass, and J. W. Rich-Edwards Plasma C-Reactive Protein in Early Pregnancy and Preterm Delivery Am. J. Epidemiol., December 1, 2005; 162(11): 1108 - 1113. [Abstract] [Full Text] [PDF]

				S. Black, I. Kushner, and D. Samols C-reactive Protein J. Biol. Chem., November 19, 2004; 279(47): 48487 - 48490. [Abstract] [Full Text] [PDF]

				K. B. Bodman-Smith, R. E. Gregory, P. T. Harrison, and J. G. Raynes Fc{gamma}RIIa expression with Fc{gamma}RI results in C-reactive protein- and IgG-mediated phagocytosis J. Leukoc. Biol., June 1, 2004; 75(6): 1029 - 1035. [Abstract] [Full Text] [PDF]

				C. Mold, W. Rodriguez, B. Rodic-Polic, and T. W. Du Clos C-Reactive Protein Mediates Protection from Lipopolysaccharide Through Interactions With Fc{gamma}R J. Immunol., December 15, 2002; 169(12): 7019 - 7025. [Abstract] [Full Text] [PDF]

				A. Papafili, M. R. Hill, D. J. Brull, R. J. McAnulty, R. P. Marshall, S. E. Humphries, and G. J. Laurent Common Promoter Variant in Cyclooxygenase-2 Represses Gene Expression: Evidence of Role in Acute-Phase Inflammatory Response Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1631 - 1636. [Abstract] [Full Text] [PDF]

				H. Nakamura, L. A. Herzenberg, J. Bai, S. Araya, N. Kondo, Y. Nishinaka, L. A. Herzenberg, and J. Yodoi Circulating thioredoxin suppresses lipopolysaccharide-induced neutrophil chemotaxis PNAS, December 6, 2001; (2001) 191498798. [Abstract] [Full Text] [PDF]

				C. Zouki, B. Haas, J. S. D. Chan, L. A. Potempa, and J. G. Filep Loss of Pentameric Symmetry of C-Reactive Protein Is Associated with Promotion of Neutrophil-Endothelial Cell Adhesion J. Immunol., November 1, 2001; 167(9): 5355 - 5361. [Abstract] [Full Text] [PDF]

				K. Balto, H. Sasaki, and P. Stashenko Interleukin-6 Deficiency Increases Inflammatory Bone Destruction Infect. Immun., February 1, 2001; 69(2): 744 - 750. [Abstract] [Full Text] [PDF]

				J. S. Solomkin Use of knockouts to define sequential steps on a pathway to organ injury: Focus on "Essential role for IL-6 in postresuscitation inflammation in hemorrhagic shock" Am J Physiol Cell Physiol, February 1, 2001; 280(2): C237 - C238. [Full Text] [PDF]

				M.-P. Stein, C. Mold, and T. W. Du Clos C-Reactive Protein Binding to Murine Leukocytes Requires Fc{gamma} Receptors J. Immunol., February 1, 2000; 164(3): 1514 - 1520. [Abstract] [Full Text] [PDF]

				R. M. Heuertz, S. M. Tricomi, U. R. Ezekiel, and R. O. Webster C-reactive Protein Inhibits Chemotactic Peptide-induced p38 Mitogen-activated Protein Kinase Activity and Human Neutrophil Movement J. Biol. Chem., June 18, 1999; 274(25): 17968 - 17974. [Abstract] [Full Text] [PDF]

				C. Gabay and I. Kushner Acute-Phase Proteins and Other Systemic Responses to Inflammation N. Engl. J. Med., February 11, 1999; 340(6): 448 - 454. [Full Text] [PDF]

				S. A. Jones, D. Novick, S. Horiuchi, N. Yamamoto, A. J. Szalai, and G. M. Fuller C-reactive Protein: A Physiological Activator of Interleukin 6 Receptor Shedding J. Exp. Med., February 1, 1999; 189(3): 599 - 604. [Abstract] [Full Text] [PDF]

				E. Ayroldi, O. Zollo, L. Cannarile, F. D' Adamio, U. Grohmann, D. V. Delfino, and C. Riccardi Interleukin-6 (IL-6) Prevents Activation-Induced Cell Death: IL-2-Independent Inhibition of Fas/fasL Expression and Cell Death Blood, December 1, 1998; 92(11): 4212 - 4219. [Abstract] [Full Text] [PDF]

				W. Zhong, Q. Zen, J. Tebo, K. Schlottmann, M. Coggeshall, and R. F. Mortensen Effect of Human C-Reactive Protein on Chemokine and Chemotactic Factor-Induced Neutrophil Chemotaxis and Signaling J. Immunol., September 1, 1998; 161(5): 2533 - 2540. [Abstract] [Full Text] [PDF]

				O. MICHEL, A.-M. NAGY, M. SCHROEVEN, J. DUCHATEAU, J. NEVE, P. FONDU, and R. SERGYSELS Dose-Response Relationship to Inhaled Endotoxin in Normal Subjects Am. J. Respir. Crit. Care Med., October 1, 1997; 156(4): 1157 - 1164. [Abstract] [Full Text] [PDF]

				C. CASALS, A. VARELA, M. L. F. RUANO, F. VALIÑO, J. PÉREZ-GIL, N. TORRE, E. JORGE, F. TENDILLO, and J. L. CASTILLO-OLIVARES Increase of C-Reactive Protein and Decrease of Surfactant Protein A in Surfactant after Lung Transplantation Am. J. Respir. Crit. Care Med., January 1, 1997; 157(1): 43 - 49. [Abstract] [Full Text]

				H. Nakamura, L. A. Herzenberg, J. Bai, S. Araya, N. Kondo, Y. Nishinaka, L. A. Herzenberg, and J. Yodoi Circulating thioredoxin suppresses lipopolysaccharide-induced neutrophil chemotaxis PNAS, December 18, 2001; 98(26): 15143 - 15148. [Abstract] [Full Text] [PDF]