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278 Schirato et al. | Journal of Clinical and Translational Research 2024; 10(5): 269-282
enhancing the inflammatory process. From this more orthodox Platelets, once regarded as a thrombus-forming agent, are now
standpoint, increased neutrophil count and activation would act recognized as primary players in inflammatory processes.
as pro-inflammatory agents. Activated platelets produce platelet-derived MPs that induce
However, neutrophils play an anti-inflammatory role in many neutrophil clustering and further activation [45,61]. Similarly,
instances. Neutrophil-derived MPs are potential inhibitors endothelial-derived MPs induce neutrophil adhesion and
of macrophage activation [57]. For instance, annexin-1-rich activation [62]. Therefore, an inflammatory process can
neutrophil-derived MPs inhibit neutrophil activation [58], become self-sustaining, as the activation of one cell type leads
downregulating an inflammatory response. The production to the activation of another, which in turn further activates the
of platelet activation factors depends on the neutrophils’ original cell type. In such a setting, an intriguing phenomenon
state; it occurs when neutrophils are adherent (i.e., under a may occur: Despite being activated and having a tendency
stimulated condition) but not when they are in suspension [44]. for neutrophilia, the neutrophil count might decrease due to
Neutrophil-derived MPs are not a homogeneous set, and they migration/sequestration in damaged tissues [63,64]. In other
can induce or inhibit inflammation [59]. Besides this functional words, the inflammatory condition might appear, without
diversity, variations in neutrophil counts might lead to different changes in neutrophil count.
outcomes. For instance, an increase in neutrophil count seems Considering HRV as an index of physiological stress from
to be associated with benign prostate enlargement, whereas a various sources, our results, along with other reports [18,32],
decrease might indicate a malignant case [60]. Exercise-induced suggest the putative illustration depicted in Figure 10. The
neutrophilia illustrates the challenge of defining a consistent initial phase of decompression leads to a certain degree of
pattern in response to physical effort, as reports of neutrophil bubble formation and inflammatory response activation [65].
counts in peripheral blood vary widely. In our previous Subsequently, depending on the decompression rate, one of
study [19], the MPO MFI, an important marker of neutrophil three outcomes may occur, as modeled in a dynamical system
activation, demonstrated a negative correlation with the number by Schirato et al. [65], which represent the interactions of
of circulating neutrophils (−0.55), and a significant positive supersaturation, bubble production, inflammation, and their
correlation with the percentage of granulocytes expressing respective feedbacks.
MPO on the membrane surface (0.7). A negative correlation In the case of elevated overall supersaturation, increased
between neutrophil-derived MPs (CD66b+) and MPO MFI tissue damage and bubble formation occur, resulting in positive
was also observed (−0.32). These results suggest that increased inflammatory feedback [66,67]. At the end of the decompression
circulating neutrophil counts are not necessarily indicative of process, a state of high physiological stress with an important
their activation or associated inflammatory processes. inflammatory process in progress is likely to be observed. In
It is also important to consider the role of platelet- and this case, subjects will most probably develop decompression
endothelial-derived MPs and their interactions with neutrophils. sickness [68].

Figure 11. Possible schematics of the immune system response to decompression, with platelet- and endothelial-derived MPs are referred to as pMPs
and eMPs, respectively
Abbreviation: MP: Microparticle; pMPs: Platelet microparticles; eMPs: Endothelial microparticles
DOI: https://doi.org/10.36922/jctr.24.00021