Mast Cell Tryptase and Implications for SARS-CoV-2 Pathogenesis

Mast cells (MCs) are heterogenous innate leukocytes producing many inflammatory mediators during viral infections that can be protective or damaging to the host, as is seen in the infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen responsible for the coronavirus disease that was first identified in 2019 (COVID-19). MCs can sense viruses by diverse mechanisms. They express angiotensin-converting enzyme 2 (ACE2), known as the principal entry receptor for SARS-CoV-2, and tryptase that can promote SARS-CoV-2 infection. Tryptase is one of the most abundant serine proteases released by MCs during degranulation and is reported to have both beneficial and detrimental roles in respiratory diseases. Reviewed here are the potential roles of MC-derived tryptase during COVID-19, the implications it has in the pathogenesis of SARS-CoV-2, and the possibility of treating COVID-19 by targeting tryptase.

Assessment of Nerve Repair Augmented with Adipose-Derived Mast Cells in an Animal Model

We aimed to analyze the involvement of adipose-sourced mast cells in nerve repair. Sixteen Wistar rats underwent complete transection of the sciatic nerves followed by either direct neurorrhaphy or neurorrhaphy and processed abdominal fat. Four animals were used as controls. Specimens were obtained at 4 and 10 weeks and analyzed using luxol fast blue stain, mast cell tryptase and CD34 (for angiogenesis) per microscopic field ×200. When assessed by luxol fast blue, normal nerves showed an average of 2–3 mast cells/field. At 4 weeks, there were 9.25 for the simple nerve sutures and 16 for the augmented repairs. At 10 weeks, there were 23 and 27.6. When assessed by mast cell tryptase, there were no positives in the controls. At 4 weeks, we found an average of 4 in the simple sutures and 2.5 in the augmented repairs. At 10 weeks, there were 4.5 and 0.2. In controls, there were 1–2 CD34+ blood vessels per field. At 4 weeks, simple repairs showed an average of 4 and, in those with adipose addition, 5.5. At 10 weeks, there were 7 and 12. Mechanically processed adipose tissue augmented nerve repair does not seem to increase mast cell expression but may support angiogenesis in an experimental model.

Mast cells in luminal vs non-luminal breast cancers

Background: Tumor growth and development is determined by the mutual interaction between the cancer cells themselves and the microenvironment. It contains various elements, including immune cells. Of all, mast cells have one of the most controversial roles. The aim of the present study was to evaluate the expression of mast cell tryptase in the luminal and non-luminal subtypes of breast cancer and establish a possible link between infiltration with MCs and expression of hormone receptors. Material and methods: The experimental study included 80 cases of breast carcinomas that were analyzed immunohistochemically in order to establish the molecular profile and the expression of tryptase, a specific marker of mast cells. The data were processed using the SPSS program. Pearson’s coefficient (r) and the other values were considered statistically significant in case of p≤0.05. Results: Both intratumoral mast cells (MCit) and peritumoral mast cells (MCpt) correlated with the expression of hormone receptors for estrogen (ER) and progesterone (PR). Thus, the following relations were established: MCit and ER (r=0.343, p=0.002), MCpt and ER (r=0.394, p=0.000295) and MCpt and PR (r=0.386, p=0.000409). Statistically significant correlations between HER2 expression and mast cells content have not been established. Conclusions: Mast cells invasion, peri- and intratumoral, is strongly influenced by the expression of hormone receptors. The luminal subtypes of breast cancer are characterized by a higher density of mast cells.

4 Histamine, mast cell tryptase and post-exercise hypotension in healthy and collapsed marathon runners

IntroductionHeat stress exacerbates post-exercise hypotension and cardiovascular disturbances from elevated body temperature and may contribute to exertion-related incapacity. Mast cell degranulation and muscle mass are considered likely modifiers, though this hypothesis lacks practical evidence. This study had three aims: 1) to characterise pre-post responses in histamine and mast cell tryptase (MCT); 2) to investigate relationships between whole body muscle mass (WBMM) and changes in blood pressure post marathon; 3) to identify any differences in runners incapacitated from marathon running.Methods24 recreational runners were recruited and successfully completed the 2019 Brighton Marathon (COMPLETION). WBMM was measured by bioimpedance at rested baseline. A further eight participants were recruited from incapacitated runners diagnosed with heat illness (COLLAPSE). Histamine, MCT, blood pressure, heart rate, body temperature and echocardiographic measures were taken before and after exercise (COMPLETION) and upon hyperthermic incapacitation (COLLAPSE).ResultsIn COMPLETION, MCT increased by nearly 50% from baseline (p=0.001), whereas histamine and body temperature did not vary (P>0.9462). Systolic (sBP), diastolic (dBP) and mean (MAP) arterial blood pressures and systemic vascular resistance (SVR) declined (p<0.019). WBMM negatively correlated with ΔsBP (r=-0.43, p=0.046). For COLLAPSE versus COMPLETION there were significant elevations in MCT (1769±244 ng/L vs 1179±431, p=0.001) and body temperature (39.8±1.3 vs 36.2±0.8°C, p<0.0001) with a non-significant rise in histamine (9.6±17.9μg/L vs 13.7±33.9, p=0.1074) and significantly lower MAP, dBP and SVR (p<0.0327).ConclusionsThese data support the hypothesis that mast cell degranulation is a vasodilatory mechanism underlying PEH and exercise associated collapse. The magnitude of PEH is inversely proportional to the muscle mass and enhanced by concomitant body heating.