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Updated: Jun 22, 2026
Lumican Extraction from Amniotic Membrane and Determination of its Storage Temperature
Published on: October 14, 2022
Extracellular matrix lumican deposited on the surface of neutrophils promotes migration by binding to beta2 integrin
Seakwoo Lee1, Kyle Bowrin, Abdel Rahim Hamad
1Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Abstract:
During inflammation, circulating polymorphonuclear neutrophils (PMNs) receive signals to cross the endothelial barrier and migrate through the extracellular matrix (ECM) to reach the injured site. Migration requires complex and poorly understood interactions of chemokines, chemokine receptors, ECM molecules, integrins, and other receptors. Here we show that the ECM protein lumican regulates PMN migration through interactions with specific integrin receptors. Lumican-deficient (Lum(-/-)) mice manifest connective tissue defects, impaired innate immune response, and poor wound healing with reduced PMN infiltration. Lum(-/-) PMNs exhibit poor chemotactic migration that is restored with exogenous recombinant lumican and inhibited by anti-lumican antibody, confirming a role for lumican in PMN migration. Treatment of PMNs with antibodies that block beta(2), beta(1), and alpha(M) integrin subunits inhibits lumican-mediated migration. Furthermore, immunohistochemical and biochemical approaches indicate binding of lumican to beta(2), alpha(M), and alpha(L) integrin subunits. Thus, lumican may regulate PMN migration mediated by MAC-1 (alpha(M)/beta(2)) and LFA-1 (alpha(L)/beta(2)), the two major PMN surface integrins. We detected lumican on the surface of peritoneal PMNs and not bone marrow or peripheral blood PMNs. This suggests that PMNs must acquire lumican during or after crossing the endothelial barrier as they exit circulation. We also found that peritoneal PMNs do not express lumican, whereas endothelial cells do. Taken together these observations suggest a novel endothelial lumican-mediated paracrine regulation of neutrophils early on in their migration path.
Insights
The extracellular matrix protein lumican regulates polymorphonuclear neutrophil (PMN) migration by interacting with integrin receptors. Endothelial cells provide lumican to PMNs, facilitating their movement during inflammation and wound healing.
Area of Science:
- Immunology
- Cell Biology
- Extracellular Matrix Biology
Background:
- Polymorphonuclear neutrophils (PMNs) migrate through the extracellular matrix (ECM) to sites of injury during inflammation.
- This migration is a complex process involving chemokines, receptors, and ECM molecules, with specific regulatory mechanisms remaining poorly understood.
Purpose of the Study:
- To investigate the role of the ECM protein lumican in regulating PMN migration.
- To elucidate the interaction between lumican and integrin receptors during neutrophil transmigration.
Main Methods:
- Utilized lumican-deficient (Lum(-/-)) mice to assess PMN infiltration and wound healing.
- Performed chemotaxis assays with PMNs treated with recombinant lumican or anti-lumican antibodies.
- Investigated lumican binding to specific integrin subunits (beta(2), beta(1), alpha(M), alpha(L)) using biochemical and immunohistochemical approaches.
- Examined lumican expression on PMNs from different sources (peritoneal, bone marrow, peripheral blood) and on endothelial cells.
Main Results:
- Lumican-deficient mice exhibited impaired innate immune response, poor wound healing, and reduced PMN infiltration.
- Lumican-deficient PMNs showed defective chemotactic migration, which was restored by exogenous lumican and blocked by anti-lumican antibodies.
- Lumican was found to bind to beta(2), alpha(M), and alpha(L) integrin subunits, suggesting a role in MAC-1 and LFA-1 mediated migration.
- Lumican was detected on peritoneal PMNs but not in bone marrow or peripheral blood PMNs, and was expressed by endothelial cells, not peritoneal PMNs.
Conclusions:
- Lumican is a key regulator of PMN migration through interactions with integrin receptors.
- Endothelial cells likely provide lumican in a paracrine manner to facilitate early neutrophil migration.
- This identifies a novel mechanism of endothelial lumican-mediated regulation of neutrophil recruitment to inflammatory sites.
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