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Veterinary immunology and immunopathology2003; 91(2); 119-134; doi: 10.1016/s0165-2427(02)00287-8

Equine platelet CD62P (P-selectin) expression: a phenotypic and morphologic study.

Abstract: Acute inflammatory diseases, such as colic, septicemia and endotoxemia are common in equines and have been shown to be correlated to vascular injury and thrombosis. In humans with similar thrombotic conditions, P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1)-mediated platelet-leukocyte adhesion contributes to the pathogenesis of these disorders through the generation of inflammatory mediators and tissue factor. As such, we hypothesized that a P-selectin-PSGL-1 (platelet-leukocyte) interaction, similar to that in humans, may also exist in the horse. The objective of this study was to investigate phenotypic and morphological properties of equine platelet activation with a focus on CD62P (P-selectin) expression and CD62P mediated platelet-leukocyte interactions. To study high levels of platelet activation, we used 1 U/ml thrombin to induce secondary, irreversible aggregation in both human and equine platelets. Addition of glycyl-L-prolyl-L-arginyl-L-proline amide (GPRP) prior to thrombin activation blocked fibrin polymerization, allowing the use of flow cytometry to study alpha-granule expression as a measure of platelet activation. Thrombin activation resulted in high levels of activation, measured as P-selectin expression, in both humans and equines. Interestingly, our research illustrates that in healthy horses, P-selectin is also constitutively expressed on 20-25% of resting platelets. This finding is in direct contrast to humans, in which P-selectin expression is negligible (<5%) in the absence of agonist activation. The high baseline level of P-selectin expression among equine platelets may suggest that they are primed for leukocyte adhesion, possibly resulting in prothrombotic conditions. This phenomenon could be of significant clinical relevance, as it may be related to the rapid clinical decline often seen in equine patients with colic and endotoxemia, where vascular injury and thrombotic complications compromise patient survival. Based on these findings, further investigation into the mechanisms of platelet P-selectin-mediated inflammation and platelet-leukocyte mediated vascular injury in the horse appears warranted.
Publication Date: 2003-01-25 PubMed ID: 12543548DOI: 10.1016/s0165-2427(02)00287-8Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research article investigates the possible linkages between P-selectin and equine platelet activation. The study found that P-selectin, which is widely expressed in equines but negligibly in humans, may contribute to the prothrombotic conditions that are often observed in horses suffering from colic and endotoxemia.

Study Premise

  • The research highlights common acute inflammatory diseases in equines, such as colic and septicemia. These conditions are often associated with vascular injury and thrombosis.
  • In humans who experience similar thrombotic conditions, an interaction between P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) causes platelet-leukocyte adhesion that generates inflammatory mediators and tissue factor, contributing to the pathogenesis of these disorders.
  • The study hypothesizes a similar P-selectin-PSGL-1 (platelet-leukocyte) interaction in horses.

Research Objectives

  • The study aimed to explore the phenotypic and morphological properties of equine platelet activation, with emphasis on CD62P (P-selectin) expression and its mediated platelet-leukocyte interactions.
  • The researchers sought to study high levels of platelet activation in both humans and equines through the use of 1 U/ml thrombin, an enzyme that induces irreversible platelet aggregation.
  • The study also explored the use of flow cytometry to study alpha-granule expression as a possible measure of platelet activation.

Key Findings

  • The study discovered that thrombin activation results in high levels of P-selectin expression in both humans and equines, suggesting significant platelet activation.
  • Surprisingly, the researchers found out that healthy horses constitutively express P-selectin on 20-25% of resting platelets. This is in sharp contrast to humans, where P-selectin expression is minimal (<5%) in the absence of agonist activation.
  • This higher baseline of P-selectin expression among equine platelets may suggest that they are primed for leukocyte adhesion, which may lead to prothrombotic conditions.

Implications of Findings

  • These findings may have significant clinical implications due to their possible association with the rapid clinical decline often observed in equine patients suffering from colic and endotoxemia. In such situations, vascular injury and thrombotic complications often compromise patient survival.
  • The study recommends further investigation into the mechanisms of platelet P-selectin-mediated inflammation and platelet-leukocyte mediated vascular injury in horses in order to help inform therapeutic interventions and improve patient outcomes.

Cite This Article

APA
Lalko CC, Deppe E, Ulatowski D, Lutgen A, Hart AP, Patton EA, Lunn DP, Suresh M, Darien BJ. (2003). Equine platelet CD62P (P-selectin) expression: a phenotypic and morphologic study. Vet Immunol Immunopathol, 91(2), 119-134. https://doi.org/10.1016/s0165-2427(02)00287-8

Publication

ISSN: 0165-2427
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 91
Issue: 2
Pages: 119-134

Researcher Affiliations

Lalko, Cory C
  • Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706-1102, USA.
Deppe, Elisabeth
    Ulatowski, Dan
      Lutgen, Amy
        Hart, Arlene P
          Patton, Elisabeth A
            Lunn, D Paul
              Suresh, M
                Darien, Benjamin J

                  MeSH Terms

                  • Animals
                  • Antibody Specificity
                  • Blood Platelets / drug effects
                  • Blood Platelets / metabolism
                  • Flow Cytometry
                  • Gene Expression
                  • Horses / blood
                  • Humans
                  • Leukocytes / metabolism
                  • P-Selectin / analysis
                  • Platelet Aggregation
                  • Thrombin / pharmacology
                  • Time Factors

                  Citations

                  This article has been cited 3 times.
                  1. Theuerkauf K, Obach-Schröck C, Staszyk C, Moritz A, Roscher KA. Activated platelets and platelet-leukocyte aggregates in the equine systemic inflammatory response syndrome. J Vet Diagn Invest 2022 May;34(3):448-457.
                    doi: 10.1177/10406387221077969pubmed: 35168432google scholar: lookup
                  2. Johnson CA Jr, Snyder TA, Woolley JR, Wagner WR. Flow cytometric assays for quantifying activated ovine platelets. Artif Organs 2008 Feb;32(2):136-45.
                  3. Xu J, Lasry JB, Svaren J, Wagner B, Darien BJ. Identification of equine P-selectin glycoprotein ligand-1 (CD162). Mamm Genome 2005 Jan;16(1):66-71.
                    doi: 10.1007/s00335-004-2348-6pubmed: 15674735google scholar: lookup