Howard R. Katz

Department of Medicine
Division of Rheumatology, Immunology and Allergy
Brigham & Women's Hospital
Smith Building, Room 638A
1 Jimmy Fund Way
Boston MA 02115
Tel: 617-525-1307
Fax: 617-525-1308
email:hrkatz@mbcrr.harvard.edu
2 Postdoctoral Fellows

Mast cells are responsible for the manifestations of allergy and contribute significantly to the pathogenesis of asthma and other types of inflammation. When activated, mast cells release a large number of proinflammatory mediators, including histamine, leukotrienes, prostaglandins, and cytokines. This laboratoryÕs current focus is on the gp49 family of cell surface receptors that are expressed on mast cells, neutrophils, macrophages, natural killer cells, and T cells. We have identified by molecular approaches 3 members of the gp49 family that are derived from 2 genes (1,2). These studies revealed that one of the members, gp49B1, has two Òimmunoreceptor tyrosine-based inhibitory motifsÓ (ITIMs). We then established that gp49B1 inhibits IgE-mediated activation of mast cells in vitro (3), defined the signal transduction pathway involved in the gp49B1-mediated inhibition (4), and identified the integrin avb3 as a ligand for gp49B1 in vitro (5). We have also created gp49B1 null mice by targeted disruption of the gp49B gene, and established that gp49B1 is an endogenous inhibitor of mast cell and neutrophil activation elicited in vivo through signals from the innate and adaptive immune systems (6-8). The mechanism(s) by which gp49B1 inhibits mast cell and neutrophil activation in vivo is a major area of investigation, as is the role of gp49B1 in regulating the outcomes of several models of inflammatory diseases (9). Our studies have established a novel counter-regulatory pathway by which cell activation is inhibited in situ, and which may provide a new therapeutic target for the inhibition of inflammatory diseases.

Papers & Publications:

1. M. C. Castells, L. B. Klickstein, K. Hassani, Cumplido J.A., M. E. Lacouture, K. F. Austen, and H. R. Katz. gp49B1-avb3 interaction inhibits antigen-induced mast cell activation. Nature Immunol. 2:436-442, 2001.
2. M. Daheshia, D. S. Friend, M. J. Grusby, K. F. Austen, and H. R. Katz. Increased severity of local and systemic anaphylactic reactions in gp49B1-deficient mice. J.Exp.Med. 194:227-233, 2001.
3. A. F. Feldweg, D. S. Friend, J. S. Zhou, Y. Kanaoka, M. Daheshia, L. Li, K. F. Austen, and H. R. Katz. gp49B1 suppresses stem cell factor-induced mast cell activation-secretion and attendant inflammation in vivo. Eur.J.Immunol. In Press, 2003.
4. J. S. Zhou, D. S. Friend, A. F. Feldweg, M. Daheshia, L. Li, K. F. Austen, and H. R. Katz. Prevention of lipopolysaccharide-induced microangiopathy by gp49B1: Evidence for an important role for gp49B1 expression on neutrophils. J.Exp.Med. 198:1243-1251, 2003.
5. J. S. Zhou, D. S. Friend, D. M. Lee, L. Li, K. F. Austen, and H. R. Katz. gp49B1 deficiency is associated with increases in cyokine and chemokine production and severity of proliferative synovitis induced by anti-type II collagen mAb. Eur.J.Immunol. 35:1530-1538, 2005