Transport of serum IgA into murine respiratory secretions and its implications for immunization strategies.
Both nonlabeled and radiolabeled IgA mAb with specificity toward Sendai virus, a respiratory pathogen, were used to investigate the transport of serum polymeric and monomeric IgA into murine upper and lower respiratory secretions as well as into the gut. After purification by affinity chromatography, IgA mAb were fractionated into monomers and polymers by gel filtration and radiolabeled with 125I. Mice were injected i.v. with either 125I-monomer and 131I-albumin or 125I-polymer and 161I-albumin. At various times after injection, serum and gut, nasal and bronchoalveolar lavage samples were collected. The TCA precipitable radioactivities were determined and the selective transport indices calculated. The results indicated selective transport of polymeric IgA but not monomeric IgA from serum into upper respiratory and intestinal secretions. The degree of TCA precipitability in nasal lavage and to a lesser extent gut secretions suggested significant degradation of the antibody during or after transport. To investigate further the integrity of the IgA in mucosal secretions, ELISA viral binding activity of nonradiolabeled IgA was determined for both IgA incubated with nasal secretions in vitro and polymeric IgA recovered by nasal lavage 4 h after i.v. injection. Although reconstitution experiments indicated no significant loss of antibody binding activity after incubation of antibody with lavage fluid in vitro, only negligible ELISA binding activity was detected in nasal washes after i.v. injection of antibody. The data overall suggest that although there is a quantitatively small, but selective transport of polymeric IgA into the upper respiratory tract, this transport results in minimal functional antibody activity. Implications of these and other findings for strategies of oral immunization in prophylaxis against respiratory infections are discussed.
Mazanec
M B
MB
Department of Pathology, Case Western Reserve University, Cleveland, OH 44106.
Nedrud
J G
JG
Liang
X P
XP
Lamm
M E
ME
D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000032:analysis / Q000502:physiology*; D001693:Biological Transport, Active; D007070:Immunoglobulin A / Q000008:administration & dosage / Q000032:analysis / Q000502:physiology*; D007419:Intestinal Secretions / Q000032:analysis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009297:Nasal Mucosa / Q000032:analysis / Q000378:metabolism; D010222:Parainfluenza Virus 1, Human / Q000276:immunology; D011108:Polymers; D011869:Radioligand Assay; D012137:Respiratory System / Q000276:immunology / Q000378:metabolism*; D012141:Respiratory Tract Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control*
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D011108:Polymers