Distribution and partial characterisation of IgG Fc binding protein in various mucin producing cells and body fluids.
OBJECTIVE
Mucus released from goblet cells is important in intestinal mucosal defence, and mucin glycoproteins are thought to be major components of mucus. Recently, we identified and cloned another component of human colonic mucus, IgG Fc binding protein (Fc gamma BP). Fc gamma BP is immunologically distinct from known Fc gamma receptors and its structure contains repeated cysteine rich unit sequences resembling those present in mucins. In this work, we assessed the tissue distribution of Fc gamma BP, its binding activity in various body fluids, and its ability to inhibit complement mediated haemolysis.


METHODS
Immunohistochemical localisation of Fc gamma BP, using monoclonal antibodies against Fc gamma BP (K9 or K17) and labelled IgG, was conducted in various mucin producing tissues: colon, small intestine, stomach, gall bladder, cystic duct, choledochus, bronchus, submandibular gland, conjunctiva, and cervix uteri. The binding activity of Fc gamma BP in mucus extracted from colon, gastric juice, bile, nasal discharges, saliva, sputum, and tears was also examined by immunodotblot and immunoprecipitation using these monoclonal antibodies. Inhibition of complement mediated haemolysis by Fc gamma BP was investigated using sheep red blood cells (SRBC) and anti-SRBC IgG.


RESULTS
The immunohistochemical study revealed that mucin secreting cells in the colon, small intestine, gall bladder, cystic duct, choledochus, bronchus, submandibular gland, and cervix uteri contained Fc gamma BP, and immunodotblot and immunoprecipitation analysis using IgG and monoclonal antibodies demonstrated that the fluids secreted by these cells were capable of binding IgG. Mucin producing cells of the conjunctiva did not express Fc gamma BP molecules or bind to IgG. The surface mucus cells in the stomach were variably positive for Fc gamma BP. Perhaps because of proteolytic degradation, Fc gamma BP in gut lavage fluid did not have IgG binding activity, although this activity was present in the mucus covering the colon. Fc gamma BP suppressed complement mediated haemolysis of SRBC.


CONCLUSIONS
Fc gamma BP is widely expressed on mucosal surfaces and in external secretions. It is functionally intact in several fluids. These findings lend support to the concept that Fc gamma BP is an important component of mucosal immunological defences.
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
K
K
Kobayashi
H
H
Ogata
M
M
Morikawa
S
S
Iijima
N
N
Harada
T
T
Yoshida
W R
WR
Brown
N
N
Inoue
Y
Y
Hamada
H
H
Ishii
M
M
Watanabe
T
T
Hibi
D000818:Animals; D001826:Body Fluids / Q000276:immunology; D003165:Complement System Proteins / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007150:Immunohistochemistry / Q000379:methods; D007413:Intestinal Mucosa / Q000276:immunology*; D008222:Lymphokines / Q000032:analysis* / Q000378:metabolism; D009093:Mucus / Q000276:immunology*; D009928:Organ Specificity; D011233:Precipitin Tests; D029584:Prostatic Secretory Proteins; D011485:Protein Binding; D012756:Sheep
D007141:Immunoglobulin Fc Fragments; D008222:Lymphokines; D029584:Prostatic Secretory Proteins; C043076:beta-microseminoprotein; C013059:immunoglobulin-binding factors; D003165:Complement System Proteins