Neutrophils and the calcium-binding protein MRP-14 mediate carrageenan-induced antinociception in mice

Background: We have previously shown that the calcium-binding protein MRP-14 secreted by neutrophils mediates the antinociceptive response in an acute inflammatory model induced by the intraperitoneal injection of glycogen in mice.Aim: In an attempt to broaden the concept that neutrophils and MRP-14 controls inflammatory pain induced by different type of irritants, in the present study, after demonstrating that carrageenan (Cg) also induces atinociception in mice, we investigated the participation of both neutrophils and MRP-14 in the phenomenon.Methods: Male Swiss mice were injected intraperitoneally with Cg and after different time intervals, the pattern of cell migration of the peritoneal exudate and the nociceptive response of animals submitted to the writhing test were evaluated. The participation of neutrophils and of the MRP-14 on the Cg effect was evaluated by systemic inoculation of monoclonal antibodies anti-granulocyte and anti-MRP-14.Results: Our results demonstrate that the acute neutrophilic peritonitis evoked by Cg induced antinociception 2, 4 and 8 h after inoculation of the irritant. Monoclonal antibodies anti-granulocyte or anti-MRP-14 reverts the antinociceptive response only 2 and 8 h after Cg injection. The antibody anti-MRP-14 partially reverts the antinociception observed after 4 h of Cg injection while the anti-granulocyte antibody enhances this effect. This effect is reverted by simultaneous treatment of the animals with both antibodies. After 4 h of Cg injection in neutrophil-depleted mice a significant expression of the calcium-binding protein MRP-14 was detected in the cytoplasm of peritoneal macrophages. This suggests that the enhancement of the effect observed after treatment with the anti-neutrophil antibody may be due to secretion of MRP-14 by macrophages. It has also been demonstrated that endogenous opioids and glucocorticoids are not involved in the antinociception observed at the 4th hour after Cg injection.Conclusion: These data support the hypothesis that neutrophils and the calcium-binding protein MRP-14 are participants of the endogenous control of inflammatory pain in mice despite the model of acute inflammation used.

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Neutrophilic Cell-Free Exudate Induces Antinociception Mediate by the Protein S100A9

Mediators of Inflammation ◽

10.1155/mi/2006/36765 ◽

2006 ◽

Vol 2006 ◽

pp. 1-6 ◽

Cited By ~ 9

Author(s):

Rosana L. Pagano ◽

Mario Mariano ◽

Renata Giorgi

Keyword(s):

Monoclonal Antibody ◽

Calcium Binding ◽

Inflammatory Pain ◽

Initial Phase ◽

Binding Protein ◽

Antinociceptive Effect ◽

Calcium Binding Protein ◽

Nociceptive Response ◽

Endogenous Control

Calcium-binding protein S100A9 (MRP-14) induces antinociceptive effect in an experimental model of painful sensibility and participates of antinociception observed during neutrophilic peritonitis induced by glycogen or carrageenan in mice. In this study, the direct antinociceptive role of the protein S100A9 in neutrophilic cell-free exudates obtained of mice injected with glycogen was investigated. Mice were intraperitoneally injected with a glycogen solution, and after4,8,24, and48hours, either the pattern of cell migration of the peritoneal exudate or the nociceptive response of animals was evaluated. The glycogen-induced neutrophilic peritonitis evoked antinociception4and8hours after inoculation of the irritant. Peritoneal cell-free exudates, collected in different times after the irritant injection, were transferred to naive animals which were submitted to the nociceptive test. The transference of exudates also induced antinociceptive effect, and neutralization of S100A9 activity by anti-S100A9 monoclonal antibody totally reverted this response. This effect was not observed when experiments were made24or48hours after glycogen injection. These results clearly indicate that S100A9 is secreted during glycogen-induced neutrophilic peritonitis, and that this protein is responsible by antinociception observed in the initial phase of inflammatory reaction. Thus, these data reinforce the hypothesis that the calcium-binding protein S100A9 participates of the endogenous control of inflammatory pain.

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Secreted modular calcium-binding protein 1 binds and activates thrombin to account for platelet hyperreactivity in diabetes

Blood ◽

10.1182/blood.2020009405 ◽

2021 ◽

Vol 137 (12) ◽

pp. 1641-1651

Author(s):

Fredy Delgado Lagos ◽

Amro Elgheznawy ◽

Anastasia Kyselova ◽

Dagmar Meyer zu Heringdorf ◽

Corina Ratiu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Monoclonal Antibodies ◽

Platelet Function ◽

Calcium Binding ◽

Transforming Growth Factor ◽

Binding Protein ◽

Calcium Binding Protein ◽

Matricellular Protein

Abstract Secreted modular calcium-binding protein 1 (SMOC1) is an osteonectin/SPARC-related matricellular protein, whose expression is regulated by microRNA-223 (miR-223). Given that platelets are rich in miR-223, this study investigated the expression of SMOC1 and its contribution to platelet function. Human and murine platelets expressed SMOC1, whereas platelets from SMOC1+/− mice did not present detectable mature SMOC1 protein. Platelets from SMOC1+/− mice demonstrated attenuated responsiveness to thrombin (platelet neutrophil aggregate formation, aggregation, clot formation, Ca2+ increase, and β3 integrin phosphorylation), whereas responses to other platelet agonists were unaffected. SMOC1 has been implicated in transforming growth factor-β signaling, but no link to this pathway was detected in platelets. Rather, the SMOC1 Kazal domain directly bound thrombin to potentiate its activity in vitro, as well as its actions on isolated platelets. The latter effects were prevented by monoclonal antibodies against SMOC1. Platelets from miR-223–deficient mice expressed high levels of SMOC1 and exhibited hyperreactivity to thrombin that was also reversed by preincubation with monoclonal antibodies against SMOC1. Similarly, SMOC1 levels were markedly upregulated in platelets from individuals with type 2 diabetes, and the SMOC1 antibody abrogated platelet hyperresponsiveness to thrombin. Taken together, we have identified SMOC1 as a novel thrombin-activating protein that makes a significant contribution to the pathophysiological changes in platelet function associated with type 2 diabetes. Thus, strategies that target SMOC1 or its interaction with thrombin may be attractive therapeutic approaches to normalize platelet function in diabetes.

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Immunohistochemical localization of S100 beta in human nervous system tumors by using monoclonal antibodies with specificity for the S100 beta polypeptide.

Journal of Histochemistry & Cytochemistry ◽

10.1177/34.8.3734419 ◽

1986 ◽

Vol 34 (8) ◽

pp. 977-982 ◽

Cited By ~ 32

Author(s):

L J Van Eldik ◽

R A Jensen ◽

B A Ehrenfried ◽

W O Whetsell

Keyword(s):

Monoclonal Antibody ◽

Nervous System ◽

Monoclonal Antibodies ◽

Calcium Binding ◽

Binding Protein ◽

Immunohistochemical Localization ◽

Calcium Binding Protein ◽

Nervous System Tumors ◽

Human Nervous System

The immunohistochemical localization of the calcium-binding protein, S100 beta, in human nervous system tumors has been examined by using a monoclonal antibody with specificity for the S100 beta polypeptide. S100 beta-specific immunoreactivity is detected in astrocytoma, glioblastoma, Schwannoma, ependymoma, and craniopharyngioma, whereas no reactivity is seen in oligodendroglioma, meningioma, neuroblastoma, or medulloblastoma. These data suggest that analysis of S100 beta localization with these monoclonal antibodies may be useful for research or diagnostic purposes.

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