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A Method for Generating Pulmonary Neutrophilia Using Aerosolized Lipopolysaccharide
Published on: December 15, 2014
LFA-1 (CD11a/CD18) triggers hydrogen peroxide production by canine neutrophils
H Lu1, C Ballantyne, C W Smith
1Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
Insights
Lymphocyte function-associated antigen-1 (LFA-1) triggers neutrophil respiratory burst via intercellular adhesion molecule-1 (ICAM-1) adhesion. This LFA-1-dependent pathway differs from Mac-1-mediated signaling, offering new insights into neutrophil activation and immune responses.
Area of Science:
- Immunology
- Cell Biology
- Integrin Signaling
Background:
- Neutrophil respiratory burst is crucial for immune defense.
- Mac-1 (CD11b/CD18) adhesion to ICAM-1 augments this response.
- The role of LFA-1 (CD11a/CD18) in triggering the respiratory burst is less understood.
Purpose of the Study:
- To investigate if LFA-1 can trigger neutrophil respiratory burst.
- To differentiate LFA-1/ICAM-1 interactions from Mac-1/ICAM-1 interactions in this process.
Main Methods:
- Developed a chimeric ICAM-1 (C1,2;H3-5) to isolate LFA-1/ICAM-1 interactions.
- Utilized canine neutrophils and L cells expressing chimeric ICAM-1.
- Analyzed hydrogen peroxide (H2O2) production under various experimental conditions.
Main Results:
- Chimeric ICAM-1 C1,2;H3-5 supported LFA-1-dependent canine neutrophil adhesion.
- This adhesion triggered rapid H2O2 production, distinct from Mac-1-mediated responses.
- LFA-1-dependent H2O2 production was rapid, less abundant, and inhibited by anti-CD11a/ICAM-1 antibodies.
Conclusions:
- Canine neutrophils use both LFA-1 and Mac-1 integrins to interact with ICAM-1 for H2O2 signaling.
- LFA-1 mediates an early-stage response independent of chemotactic stimulation.
- Mac-1 mediates a later-stage response that requires chemotactic stimulation.
Abstract:
The respiratory burst of neutrophils stimulated by chemotactic factors is markedly augmented by Mac-1-dependent adhesion such as the interaction of Mac-1 (CD11b/CD18) with intercellular adhesion molecule-1 (ICAM-1; CD54) expressed on the surface of parenchymal cells (e.g., cardiac myocytes). In the current study, we evaluate the hypothesis that lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) can also trigger the respiratory burst in neutrophils. To isolate LFA-1/ICAM-1 interactions from Mac-1/ ICAM-1 interactions, full-length chimeric ICAM-1 was developed and expressed in L cells with domains 1 and 2 from canine ICAM-1 and domains 3-5 from human ICAM-1 (C1,2;H3-5). We have shown that canine neutrophils do not bind to human ICAM-1. We demonstrated that chimeric ICAM-1 C1,2;H3-5 supported only LFA-1-dependent adhesion of canine neutrophils and that such adhesion triggered rapid onset of H2O2 production from canine neutrophils. The following seven experimental conditions distinguished LFA-1-dependent H2O2 production from Mac-1-dependent production: It did not require exogenous chemotactic stimulation; H2O2 release was more rapid, but the amount released was <40% of that mediated by Mac-1 adhesion; it was inhibited by anti-CD11a and anti-ICAM-1 antibodies; in contrast to that mediated by Mac-1, it was not inhibited by anti-CD11b antibody, neutrophil inhibitory factor (NIF), or cytochalasin B or H7. Thus, canine neutrophils seem to be able to utilize two members of the beta2 integrin family to interact with ICAM-1 and signal H2O2 production, with LFA-1 at an early stage without prior chemotactic stimulation and Mac-1 at a later stage requiring chemotactic stimulation.
