Biology subjects

Gollomp, K. L.

Publications and source records attributed to Gollomp, K. L..

3 recordsLinked to original sources

bioRxiv2025

Platelet factor 4 modulates endothelial cell antimicrobial activity to enhance bacterial clearance and improve sepsis outcomes

Sepsis is a life-threatening condition characterized by dysregulated host responses to infection. Here, we identify platelet factor 4 (PF4) as a key mediator of vascular antimicrobial defense. In vitro, PF4 enhanced endothelial cell internalization of Escherichia coli via interactions with the PF4 receptor CXCR3 and the endothelial glycocalyx, directing bacteria to clathrin-mediated endocytosis and lysosomal degradation. In vivo, PF4 administration improved survival and reduced sepsis severity, bacterial burden, inflammation, and thrombosis in wild-type (WT) and PF4 knockout (PF4-/-) mice challenged with systemic polymicrobial infection. Using intravital microscopy, we observed that infused bacteria were rapidly sequestered in the pulmonary microvasculature. However, PF4-/- mice exhibited impaired bacterial clearance and increased microvascular platelet adhesion and aggregation. In the liver, following Kupffer cell depletion, PF4-/- mice had increased sinusoidal platelet accumulation, larger bacterial aggregates, and elevated hepatic bacterial burden compared to WT controls. Collectively, these findings reveal that PF4 promotes bacterial clearance and restrains immunothrombosis during sepsis in part via endothelial cell uptake and destruction of microbes. By enhancing endothelial antimicrobial function, PF4 represents a significant yet previously underrecognized host defense mechanism that limits bacterial spread and alleviates vascular injury during infection. KEY POINTSO_LIIn vitro, PF4 accelerates bacterial clearance by enhancing endothelial uptake of bacteria and promoting their trafficking to the lysosome. C_LIO_LIIn murine sepsis, PF4 augments pathogen clearance to reduce infection severity, limit organ injury, and improve survival. C_LI

cell biology↗

bioRxiv2025

C-reactive protein and the menstrual cycle in females with sickle cell disease

There are notable sex disparities in the frequency and severity of vaso-occlusive pain episodes (VOEs) in sickle cell disease (SCD), with females experiencing more frequent and severe episodes during the reproductive years. Many individuals report a temporal link between VOEs and the menstrual cycle, suggesting that sex hormones may play a role in modulating inflammation and pain. This study explores the relationship between inflammatory markers and the menstrual cycle in females with SCD. Plasma samples from 13 female and 18 male individuals with confirmed SCD were analyzed for C-reactive protein (CRP) and other inflammatory biomarkers. In female patients, sex hormones were measured to determine the menstrual cycle phase. While no overall difference in CRP levels was observed between males and females, CRP levels fluctuated significantly across the menstrual cycle in females, with higher levels in the follicular phase compared to the luteal phase. Additionally, platelet counts were significantly elevated in females during the follicular phase compared to males. These findings suggest that cyclic inflammation may contribute to the increased frequency and severity of VOEs in females, particularly during the perimenstrual period. Further research is needed to explore whether hormonal interventions can reduce perimenstrual VOEs in SCD.

immunology↗

bioRxiv2019

Neutrophil extracellular trap stabilization leads to improved outcomes in murine models of sepsis

Sepsis is characterized by multi-organ system dysfunction that occurs due to infection. It is associated with unacceptably high morbidity and mortality and in need of improved therapeutic intervention. Neutrophils play a crucial role in sepsis, releasing neutrophil extracellular traps (NETs) composed of DNA complexed with histones and toxic antimicrobial proteins that ensnare pathogens but also damage host tissues. At presentation, patients likely have a significant NET burden contributing to the multi-organ damage. Therefore, interventions that prevent NET release would likely be ineffective at preventing NET-based injury. Treatments that enhance NET degradation may liberate captured bacteria and toxic NET degradation products (NDPs) and therefore be of limited therapeutic benefit. We propose that interventions that stabilize NETs and sequester NDPs may be protective in sepsis. Platelet factor 4 (PF4, CXCL4) a platelet-associated chemokine, binds and compacts NETs, increasing their resistance to deoxyribonuclease I. A monoclonal antibody, KKO, which binds to PF4-NET complexes, further enhances this resistance. We now show that PF4 increases NET-mediated bacterial capture in vitro, reduces the release of NDPs, and improves outcome in murine models of sepsis. An Fc-modified KKO further enhances deoxyribonuclease resistance, decreases NDP release, and increases survival in these models, supporting a novel NET-targeting approach to improve outcomes in sepsis.

immunology↗